Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction
Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction
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DOI：
10.1056/nejmoa1908655
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发表时间：
2019-10-24
影响因子：
158.5
通讯作者：
Lefkowitz, M. P.
中科院分区：
文献类型：
--
作者：
Solomon, S. D.;McMurray, J. J. V.;Lefkowitz, M. P.
背景
血管紧张素受体 - 脑啡肽酶抑制剂沙库巴曲 - 缬沙坦可降低心力衰竭且射血分数降低的患者因心力衰竭住院或心血管原因死亡的风险。血管紧张素受体 - 脑啡肽酶抑制剂在射血分数保留的心力衰竭患者中的作用尚不明确。
方法
我们将4822例纽约心脏协会（NYHA）心功能Ⅱ - Ⅳ级、射血分数45%或更高、利钠肽水平升高且有结构性心脏病的患者随机分组，分别接受沙库巴曲 - 缬沙坦（目标剂量为沙库巴曲97mg与缬沙坦103mg，每日两次）或缬沙坦（目标剂量为160mg，每日两次）治疗。主要结局是心力衰竭总住院次数和心血管原因死亡的复合指标。同时还评估了主要结局的组成部分、次要结局（包括NYHA心功能分级变化、肾功能恶化以及堪萨斯城心肌病问卷[KCCQ]临床综合评分[评分范围0 - 100，分数越高表明症状和身体受限越少]的变化）以及安全性。
结果
沙库巴曲 - 缬沙坦组526例患者中有894例主要事件，缬沙坦组557例患者中有1009例主要事件（发生率比值为0.87；95%置信区间[CI]为0.75 - 1.01；P = 0.06）。沙库巴曲 - 缬沙坦组心血管原因死亡率为8.5%，缬沙坦组为8.9%（风险比为0.95；95%CI为0.79 - 1.16）；心力衰竭总住院次数分别为690次和797次（发生率比值为0.85；95%CI为0.72 - 1.00）。沙库巴曲 - 缬沙坦组15.0%的患者NYHA心功能分级改善，缬沙坦组为12.6%（优势比为1.45；95%CI为1.13 - 1.86）；肾功能恶化分别为1.4%和2.7%（风险比为0.50；95%CI为0.33 - 0.77）。8个月时沙库巴曲 - 缬沙坦组KCCQ临床综合评分平均变化比缬沙坦组高1.0分（95%CI为0.0 - 2.1）。沙库巴曲 - 缬沙坦组患者低血压和血管性水肿发生率较高，高钾血症发生率较低。在12个预先设定的亚组中，射血分数较低的患者和女性使用沙库巴曲 - 缬沙坦可能存在异质性及潜在益处。
结论
在心力衰竭且射血分数45%或更高的患者中，沙库巴曲 - 缬沙坦并未使心力衰竭总住院次数和心血管原因死亡的发生率显著降低。（由诺华公司资助；PARAGON - HF临床试验注册号为NCT01920711）
Background The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear. Methods We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed. Results There were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P=0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril-valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril-valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women. Conclusions Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.)